Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate
Ritva Rice, … , Irma Thesleff, David P.C. Rice
Ritva Rice, … , Irma Thesleff, David P.C. Rice
Published June 15, 2004
Citation Information: J Clin Invest. 2004;113(12):1692-1700. https://doi.org/10.1172/JCI20384.
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Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate

Abstract

Classical research has suggested that early palate formation develops via epithelial-mesenchymal interactions, and in this study we reveal which signals control this process. Using Fgf10–/–, FGF receptor 2b–/– (Fgfr2b–/–), and Sonic hedgehog (Shh) mutant mice, which all exhibit cleft palate, we show that Shh is a downstream target of Fgf10/Fgfr2b signaling. Our results demonstrate that mesenchymal Fgf10 regulates the epithelial expression of Shh, which in turn signals back to the mesenchyme. This was confirmed by demonstrating that cell proliferation is decreased not only in the palatal epithelium but also in the mesenchyme of Fgfr2b–/– mice. These results reveal a new role for Fgf signaling in mammalian palate development. We show that coordinated epithelial-mesenchymal interactions are essential during the initial stages of palate development and require an Fgf-Shh signaling network.

Authors

Ritva Rice, Bradley Spencer-Dene, Elaine C. Connor, Amel Gritli-Linde, Andrew P. McMahon, Clive Dickson, Irma Thesleff, David P.C. Rice

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Molecular control of early palate development. (A) Schematic diagram sho...
Molecular control of early palate development. (A) Schematic diagram showing the mRNA expression of Fgfr2b, Fgf10, and Fgf7 in the E13 mouse palate. Fgfr2b was expressed in the oral epithelium and at a low level in the mesenchyme in the bend area between the cranial base and palatal shelf. Fgf10 and Fgf7 were also expressed at this site. In addition, Fgf10 was mainly expressed in the mesenchyme on the oral side of the developing palate and Fgf7 on the nasal aspect. In the mesenchyme adjacent to the MEE, Fgf10 and Fgf7 expression domains overlapped. “Groove” indicates the anterior-posterior groove between the palatal process and the body of the maxilla. (B) Schematic diagram illustrating the proposed Fgf10/Fgfr2b epithelial-mesenchymal interactions and possible downstream signaling in the developing palate.